Certain dibenzopyranones are useful pharmacological agents. It recently has been found that trans-1-hydroxy-3-alkyl-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[ b,d]pyran-9-ones are especially useful in the treatment of pain, anxiety, and depression, see U.S. Pat. Nos. 3,928,598, 3,944,673, and 3,953,603. Such compounds can be prepared, according to the disclosure by Fahrenholtz, Lurie and Kierstead, J. Am. Chem. Soc. 88, 2079(1966), 89, 5934(1967), by reacting a 5-alkyl resorcinol with diethyl .alpha.-acetylglutarate to form an ethyl 4-methyl-5-hydroxy-7-alkyl coumarin-3-propionate. The coumarin derivative can be reacted with a metal hydride to effect cyclization to the corresponding 1-hydroxy-3-alkyl-7,10-dihydro-6H-dibenzo-[b,d]pyran-6,9(8H)dione. Ketalization of the 9-keto group followed by reaction with methyl magnesium bromide and deketalization affords the corresponding 1-hydroxy-3-alkyl-6,6-dimethyl-6,6a,7,8-tetrahydro-9H-dibenzo[b,d]pyran-9- one. Reduction of the latter compound provides predominantly the corresponding trans-1-hydroxy-3-alkyl-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[ b,d]pyran-9-one, with minor quantities of the less active 6a,10a-cis-isomer being formed. Such process for preparing trans-dibenzopyranones suffers from being multistep and of low overall yield, in addition to requiring separation of the trans isomer from the cis isomer.
It recently has been discovered that cis-hexahydrodibenzopyranones can be converted to the corresponding trans isomer, and the cis-hexahydrodibenzopyranones can be prepared in high yield in only one step. More particularly, a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo[b,d]pyran-9-one can be reacted with an aluminum halide in an organic solvent to effect epimerization to provide the corresponding trans-hexahydrodibenzopyranone. Such process is the subject of our copending application filed this even date therewith. The reaction of a 5-substituted resorcinol with 1-methoxy-4-(1-hydroxy-1-methylethyl)-1,4-cyclohexadiene in the presence of a catalyst such as boron trifluoride diethyl etherate or stannic chloride to provide a cis-1-hydroxy-3-substituted-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibe nzo[b,d]-pyran-9-one is the subject of Day and Lavagnino's copending application filed this even date herewith.
An object of this invention is to provide an alternate process for preparing substantially exclusively cis-hexahydrodibenzo[b,d]pyran-9-ones, utilizing novel compounds which are ketals of 4-(1-hydroxy-1-methylethyl)-3-cyclohexen-1-one.